Abstract
A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzimidazoles / administration & dosage
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology*
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Diacylglycerol O-Acyltransferase / antagonists & inhibitors*
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Diacylglycerol O-Acyltransferase / metabolism
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Dose-Response Relationship, Drug
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Drug Discovery*
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Hep G2 Cells
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Humans
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Mice
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Mice, Obese
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Microsomes, Liver / enzymology
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Molecular Structure
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Obesity / drug therapy*
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Rats
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Structure-Activity Relationship
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Triglycerides / antagonists & inhibitors
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Triglycerides / metabolism
Substances
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Benzimidazoles
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Enzyme Inhibitors
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Triglycerides
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benzimidazole
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Dgat1 protein, rat
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Diacylglycerol O-Acyltransferase